Background. Presently available studies of the relationship between polymorphism of modifier genes encoding RAAS components and phenotypic manifestations in patients with hypertrophic cardiomyopathy (HCMP) provide rather inconsistent results. Aim. To identify associations between polymorphism of genes encoding RAAS components (АСЕ, AGTR1, CYP11B2, and CMA1) with the clinical phenotype of disease considering sex, age and comorbidities of patients with HCMP. Materials and methods. Analysis of clinico-demographic and instrumental data was performed for 275 patients with HCMP (97 females and 178 males aged 17 to 70; median age 51 for females and 44 for males). PCR with subsequent restriction analysis was used for amplifying the polymorphous site of studied gene. Results. The monofactorial analysis showed that the presence of episodes of unstable paroxysmal ventricular tachycardia (UVT) was associated with ID polymorphism of the ACE gene and CC polymorphism of the AGTR1 gene (p=0.008, p=0.045, respectively). The presence of atrial fibrillation (AF) had a tendency to association with CC polymorphism of the AGTR1 gene (p=0.08). Angina of high FC II–III tended to associate with GA polymorphism of the СМА1 gene (p=0.06). The multifactorial analysis showed that carriers of ID heterozygous genotype in the ACE gene more frequently had paroxysmal or constant AF forms (OR, 2.06; 1.05–4.19, 95 % CI) than carriers of other genotypes. The presence of UVT episodes was more often associated with carriers of ID genotype in the ACE gene (OR, 2.44; 1.40–4.34, 95 % CI). High FC angina was more frequently observed in carriers of ID genotype in the ACE gene (OR, 2.17; 1.18–4.10, 95 % CI) and carriers of AA genotype in the СМА1 gene (OR, 2.09; 1.05–4.29, 95 % CI). Conclusion. ID genotype of the ACE gene polymorphism is the most unfavorable factor influencing the course of HCMP in the presence of high FC angina, development of life-threatening arrhythmias and AF with an account of age and presence of concurrent stage 2–3 arterial hypertension.

Ortlepp JR, Vosberg HP, Reith S et al. Genetic polymorphisms in the rennin-angiotensin-aldosterone system associated with expression of left ventricular hypertrophy in hypertrophic cardiomyopathy: a study of five polymorphic genes in a family with a disease causing mutation in the myosin binding protein C gene. Heart. 2002 Mar;87 (3):270–5.